The monitoring of the level of endogenous analytes such as glucose, lactate, creatinine or oxygen, in certain individuals, is vitally important for their health. Certain substances such as glucose can also be administered for diagnostic stress-tests. In addition, monitoring of the level of xenobiotics such as inulin, and certain drugs and their metabolites is important for diagnosis of e.g. kidney and liver function and can be vitally important for the choice and correct dosing in drug treatment. For a chosen drug, monitoring of its pharmacokinetics under treatment conditions in a given patient can allow individualized optimization of treatment schedule and help to avoid potentially serious drug-drug interactions. For such applications a reliable device which allows monitoring of analyte concentration in body fluids such as e.g. subcutaneous interstitial fluid for several hours to a few days is necessary. To achieve acceptance from patients and non-specialized health care professionals, convenience and minimal invasiveness are extremely important features.
A convenient alternative to frequent blood sampling is to measure the concentration of the analyte in dermal interstitial fluid since the concentration of certain analytes such as e.g. glucose is highly correlated between these two fluid compartments (Bantle, et al., J Lab Clin Med 1997; 130: 436-441). Sensors for e.g. glucose monitoring in interstitial fluid are known in the art, for example U.S. Pat. No. 6,579,690, published Jun. 17, 2003 by Bonnecaze et al. Bonnecaze et al describe various embodiments of such sensor devices. One important feature of these devices as well as of devices prior in the art is that the sensor is first implanted into the body and in a second step, on the patient, has to be connected to a control unit. Such a procedure especially with miniaturized components needs a high level of skill and the use of mounting tools is complicated. These drawbacks severely limit the acceptance and can easily lead to incorrect functioning. Fully implantable sensors including wireless transmitters avoid the problems of mounting together the several components after implantation of the sensor. On the other hand, their size necessitates a surgical procedure for implantation with the associated inconveniences for the patient and needs qualified health care professionals for the implantation. The damage inflicted on the subcutaneous tissue upon implantation of the sensor results in inflammatory tissue reactions which can alter the performance of the sensor and even lead to changes in the availability of analytes surrounding the sensor. Therefore, for reliable measurements, minimal invasiveness is very important. This can only be achieved by miniaturization of the implanted parts of the sensor and optimization of the sensor shape and insertion means to avoid tissue damage upon insertion as much as possible. The sensors and insertion mechanisms of prior art are far from optimal in this respect.
To circumvent the inherent handling problems with implantable sensors, several approaches were taken to withdraw subcutaneous fluid by making holes into the skin by lancing or with a laser beam, or to withdraw fluid with an electric current. Since the volume which can be withdrawn by these means is very small, usually below 1 μl, the determination of analyte concentrations is technically difficult and not reliable and many factors, e.g. sweating can lead to changes of the composition and to massively wrong determinations.